H e m a t o lo g y E d u c a t io n - European Hematology Association

R.A. Mesa
Mayo Clinic, Scottsdale, AZ, USA
Hematology Education:
the education program for the
annual congress of the European
Hematology Association
2011;5:264-272
Myeloproliferative disorders
Individualized care plans for myelofibrosis
Introduction
Myelofibrosis (MF) in 2011 remains the
myeloproliferative neoplasm (MPN) that
induces the most morbidity and is associated
with the poorest life expectancy. 1 Although
pathogenetic origins may vary, clinically MF
is an amalgam of individuals with apparently
de novo myelofibrosis (so-called primary
myelofibrosis, or PMF), as well those who
evolved from a clear antecedent MPN, either
polycythemia vera or essential thrombocythemia
(Post ET/PV MF). 2 Regardless of
subtype of MF, patients suffer from a spectrum
of complications arising from the
malignant clone, including ineffective
hematopoiesis with resulting cytopenias,
splenomegaly, bothersome constitutional
symptoms, risk of vascular events including
thrombosis and hemorrhage, and risk of
blastic transformation. 3
A major clinical challenge for the management
of MF patients is that it is a very heterogeneous
illness in terms of symptomatic
burden, morbidity, and expected mortality.
Additionally, the clinical course can be
dynamic with certain benchmarks developing,
which can be worrisome in a previously
stable patient. An accurate assessment of
prognosis is essential in choosing the appropriate
therapy for an individual patient,
given that some patients may live more than
15 years, 4 while others, such as those who
progress to acute leukemia, have a life
expectancy as short as 2 months. 5
Historically, peripheral blood findings at
the time of diagnosis, such as anemia and
changes in leukocyte count, have been the
A B S T R A C T
Myelofibrosis (MF) is a potentially fatal myeloproliferative neoplasm (MPN) with a very heterogeneous
group of patients with widely variable prognosis. Clinical management options range from low-risk/lowreward
observation to high-risk/high-reward allogeneic stem cell transplantation. Medical therapy ranges
from off label utilization of palliative agents for MF associated anemia or splenomegaly; however, none of
these latter agents impact the natural history of the illness. The discovery of the JAK2-V617F, and subsequent
additional MPN associated mutations has led to development of a spectrum of selective inhibitors of JAK2.
Clinical trials with these latter agents have led to meaningfully reductions in MF-associated splenomegaly
and constitutional symptoms. Several additional therapies that do not directly target JAK2 (e.g., immunomodulatory
drugs, histone deacetylase inhibitors) may ameliorate MF-associated anemia and morbidity-inducing
symptoms. Balancing the potential benefits of these new agents against the risks and benefits of allogeneic
stem cell transplantation requires an accurate estimation of the prognosis for an individual patient and development
of individualized treatment plans. Evolving information regarding the efficacy of new medicines
(alone or in consolidation) will continue to modify MF treatment strategies and plans.
most prognostically significant variables in
MF, and were incorporated into the 1996
Lille criteria (Dupriez score) 6 (Table 1). In
2009, the International Working Group for
Myelofibrosis Research and Treatment
(IWG-MRT) retrospectively analyzed over
1000 cases of PMF at diagnosis and developed
a four-tier International Prognostic
Scoring System (IPSS) incorporating five factors
with independent negative prognostic
impact: age older than 65, anemia, constitutional
symptoms, leukocytosis, and circulating
blood blasts (Table 1). 3 Of these five factors,
anemia was the variable with the greatest
negative prognostic significance. 3 Further
efforts to apply the IPSS factors at any point
in time along the course of the illness resulted
in a dynamic IPSS (DIPSS), 7 which
demonstrated that the acquisition of these
factors at any point along the course of the
illness is detrimental, particularly anemia
(Table 1). Finally, within each DIPSS category
(low, intermediate-1, intermediate-2, and
high risk), three additional factors (erythrocyte
transfusion dependence, karyotype, and
the presence of thrombocytopenia) further
refines dynamic prognosis in the DIPSS-Plus
system. 8 Finally, young patients (